Autoantibodies in chronic graft versus host result from cognate T-B interactions.
A chronic graft-versus-host reaction (GVH) induced in nonautoimmune mice causes a syndrome that closely resembles SLE. In this model, donor T cells react against incompatible host Ia structures and generate excessive help, which activates a subpopulation of self-reactive B cells. We have studied whether these self-reactive B cells are activated by direct interaction with alloreactive T cells or by nonspecific bystander effects. Two types of chimeras were made: double-parental chimeras, differing at both Ia and Igh allotype [B6.C20 + bm12----(B6.C20 x bm12)F1]; and control chimeras [(B6.C20 x bm12)F1----(B6.C20 x bm12)F1]. A chronic GVH syndrome was induced in the chimeras by infusion of B6 or bm12 spleen cells. Coombs and antichromatin autoantibodies were measured using Igh allotype-specific immunoassays. The double-parental chimeras that received bm12 cells made autoantibodies principally of the Igha allotype, indicating that the bm12 T cells interacted only with the Iab-bearing host B cells. Conversely, double-parental chimeras that received B6 cells made mostly Ighb autoantibodies, indicating direct cognate interaction with the Iabm12-bearing host B cells. The control chimeras made autoantibodies of both allotypes. These results indicate that autoantibodies in chronic GVH result from direct T-B interactions and not from nonspecific T cell-derived factors.
Morris
S C
SC
Department of Microbiology/Immunology, University of North Carolina, Chapel Hill 27599.
Cheek
R L
RL
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002678:Chimera; D002843:Chromatin / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007126:Immunoglobulin Allotypes / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D002843:Chromatin; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007075:Immunoglobulin M